Esomeprazole of formula (II), the levorotatory isomer of racemic omeprazole, is an ulcer treating agent which is very effective in treating such disorders as gastric ulcer, duodenal ulcer and reflux esophagitis, which is less influenced by liver metabolism, exerting less adverse effect, as compared to the omeprazole racemate. It is now commercially available in the form of Nexium®:

Various methods of preparing esomeprazole are described in the literatures, e.g., U.S. Pat. Nos. 5,693,818 and 6,369,085, International Publication Patent Nos. WO 1996/002535, WO 1997/002261 and WO 2004/002982, Chinese Patent No. 1,087,739, [J. Deng et al., Tetrahedron: Asymmetry, 11, 1729-1732, 2000] and [H. Cotton et al., Tetrahedron: Asymmetry, 11, 3819-3825, 2000]. Among these methods, preferred in terms of commercial applicability are methods which involve resolving racemic omeprazole using an optical resolution agent or asymmetrically oxidizing a precursor of esomeprazole using a chiral reagent.
For example, Chinese Patent No. 1,087,739 discloses a method of preparing esomeprazole of formula (II) by way of reacting the racemic form of omeprazole with (S)-(−)-binol (a levorotatory isomer of β-binaphthol) as an optical resolution agent to form the inclusion complex of esomeprazole and (S)-(−)-binol of formula (I), and removing the (S)-(−)-binol moiety therefrom:

However, this method has several problems in that;
1) for the purpose of obtaining esomeprazole of a high optical purity, relatively expensive (S)-(−)-binol must be used in an excess amount of 1.5 mole equivalents based on omeprazole,
2) benzene (Class I; ICH Q3C Impurities: Guideline for Residual Solvents (CPMP/ICH/283/95)) which has potential to instigate toxicity is used as a solvent in the method,
3) the inclusion complex of formula (I), and also the solution containing same are colored pitch-black, which requires a decolorization step in the recycling of unreacted (S)-(−)-binol isolated from the reaction mixture containing the inclusion complex,
4) the removal of (S)-(−)-binol from the inclusion complex of formula (I) is performed by chromatography, which is not suitable for mass production, and
5) the optical purity of the inclusion complex of formula (I) is unsatisfactorily low, i.e., about 90% ee (enantiomeric excess), which necessitates further purification of the final esomeprazole product, causing a lowering of the yield ([J. Deng et al., Tetrahedron: Asymmetry, 11, 1729-1732, 2000]).